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KEMAS 18 (4) (2023) 473-482

Jurnal Kesehatan Masyarakat


http://journal.unnes.ac.id/nju/index.php/kemas

Types and Sources of Antioxidants that Role in Determining Fertility Level

Sri Winarni1, Ari Udijono2, Atik Mawarni1, Dharminto1, Oktavia Beni Kujariningrum1,
Waviq Azizah2
1Biostatistics and Population, Faculty of Public Health, Diponegoro University
2Epidemiology and Tropical Diseases, Faculty of Public Health, Diponegoro University

Article Info Abstract


Article History: Lifestyle and exposure to free radicals affect a person’s fertility. ROS (Reactive Oxygen
Submitted September 2022 Species) in excess can cause oxidative stress and DNA damage (deoxyribonucleic acid).
Accepted January 2023
Adequate intake of antioxidants is needed to maintain ROS levels. This review aims to
Published April 2023
determine the types and sources of antioxidants that play a role in determining a per-
Keywords: son’s fertility level. This research is a narrative review by a literature review method by
pre-testing, COVID-19 collecting and concluding data from previous studies. The search for research articles
source of antioxidants, male was carried out on Scopus, Science Direct, Clinical Key, SpringerLink, BMC, and Google
fertility, female fertility, ROS Schoolar portals with keywords foodstuffs, antioxidants, and infertility which found
8,745 articles. A total of 75 articles met the inclusion-exclusion criteria for use in writing
DOI this article. The research took time in 2022. Most antioxidants take a role in determining
https://doi.org/10.15294/
male fertility, such as glutathione, selenium, carotenoids (beta-cryptoxanthin, lycopene,
kemas.v18i4.39261
beta-carotene, and lutein), zinc, vitamin C, vitamin E, and flavonoids. NAM (Nicotina-
mide) and carvacrol play a role in determining female fertility. These antioxidants can
be found in fruits, vegetables, protein sources, and several other plants. Consumption of
antioxidant sources is highly recommended to increase fertility, especially for infertile
couples.

Introduction Lifestyle factors have a role in determining


Infertility has the potential to affect a person’s fertility (Acharya and Gowda, 2017).
various aspects of a person’s life, including Long-term exposure to chemicals, such as
physical, mental, social health, and overall pesticides, fertilizers, and industrial products
quality of life (Bakhtiyar et al., 2019). Cognitive (plasticizers and phytoestrogens) has been
reactions and emotional-affective reactions associated with decreased fertility through
to infertility conditions and the therapeutic hormonal pathways (Ding et al., 2016). Free
process are often experienced by infertile radicals had a physiological role in optimizing
patients (Hasanpoor-Azghdy et al., 2014). As sperm performance (Palmieri et al., 2016).
many as 22.3% of infertile patients had stress, Excessive amounts of ROS (reactive oxygen
with fatigue being the main complaint (38.1%). species) can cause oxidative stress and then
The duration of infertility showed a significant DNA damage (Cleaver et al., 2014). Nearly 10%
relationship with the level of stress experienced of infertile/subfertile women are identified with
by the patient (p < 0.05) (Wiweko et al., 2017). DOR (Decreased Ovarian Reserve) (Pastore et
High-stress levels allow a person to have al., 2014).
infertility three times OR=3,89; CI 95%=1,04 to The quality of the diet was related to
14,46; p=0,046) (Indarwati et al., 2017). energy and nutritional sufficiency (Mardiana


Correspondence Address: pISSN 1858-1196
Biostatistics and Population, Faculty of Public Health, Diponegoro University, Indonesia. eISSN 2355-3596
Email : winarni@live.undip.ac.id
KEMAS 18 (4) (2023) 473-482

et al., 2022). Previous research had shown that Method


healthy food intake is associated with sperm This Research is a narrative review using
and semen quality (Efrat et al., 2018). Adequate the literature review method by collecting and
intake of antioxidants is needed to maintain concluding data from previous studies. The
ROS levels (Liu et al., 2018). Antioxidants are research was conducted in April-May 2022.
compounds capable to stop the chain reaction The search for previous research articles was
of the oxidative stress process by capturing free carried out on Scopus, Science Direct, Clinical
radicals (Ko et al., 2014). Antioxidants act as Key, SpringerLink, BMC, and Google Schoolar
free radical reducers, enhancing endogenous portals with keywords in the form of foodstuffs,
antioxidant defense systems and oxidative antioxidants, and infertility. The evaluation of
stress-induced gene expression (Bai et al., 2016). the articles was carried out according to the
Antioxidant levels were significantly related to inclusion and exclusion criteria of the previous
sperm concentration and count of total motile. articles. Inclusion criteria were research
The higher of antioxidant levels in a body, the articles on the role of antioxidants in fertility
higher the sperm concentration and total motile enhancement, that can be accessed on indexed
count (Silberstein et al., 2016). Antioxidant international journal portals or national
therapy often consumed by patients is vitamin journal portals which are minimum accredited
C, vitamin E, minerals (selenium and zinc) in SINTA 2, published in 2013-2022, and was
(Bardaweel, 2014). This study will combine the an original article. The exclusion criteria are
results of various previous studies to know the an article that can be accessed in abstracts and
types and sources of antioxidants that play a proceedings only.
role in determining a person’s fertility level.

FIGURE 1. Article Selection Flowchart

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Sri Winarni, et all. / Types and Sources of Antioxidants that Role in Determining Fertility Level

A total of 584 out of 8,745 articles portal, 2 articles on the BMC journal portal,
discussed the role of antioxidants in fertility and 9 articles on the Google Schoolar with
enhancement were published from 2013-2022. minimum accredited in SINTA 2.
A total of 206 are original can be accessed
on indexed international or national journal Result and Discussion
portals that are, minimum accredited in SINTA Antioxidants have an important role in
2. A total of 131 articles can only be accessed determining a person’s fertility. Most of the
in abstract form. A total of 75 articles met antioxidants that play a role in determining male
the inclusion and exclusion criteria, so they fertility. These antioxidants include glutathione,
were used in writing this narrative review that selenium, carotenoids (beta-cryptoxanthin,
consisting of 20 articles on the Scopus journal lycopene, beta-carotene and lutein), zinc,
portal, 25 articles on the Science Direct journal vitamin C, vitamin E, and flavonoids. NAM
portal, 10 articles on the Clinical Key journal and carvacrol play a role in determining female
portal, 9 articles on the SpingerLink journal fertility.
TABLE 1. Types of Antioxidants that Play a Role in Determining a Person’s Fertility
Types of Antioxidants Role Referensi
NAM NAM is positively correlated with the rate of (Guo et al., 2022)
maturation and fertilization of mouse oocytes
Glutamine Glutamine prevents decreased sperm quality, reduces (Afolabi et al., 2022)
oxidative stress, inflammation and apoptosis
Carvacrol Carvacrol is useful in the treatment of ovarian (Sahin et al., 2022)
ischemia-reperfusion injury and infertility
β-cryptoxanthin β-cryptoxanthin has a positive effect on sperm (Haeri et al., 2022)
motility
Lycopene Lycopene can protect sperm from oxidative stress and (Babaei et al., 2021)
damage to sperm DNA
There is a positive relationship between lycopene (Zareba et al., 2013)
intake and sperm morphology
Selenium Selenium can increase semen volume and total sperm (Talebi et al., 2021)
motility
Zinc The effect of zinc supplementation through the (Shahraki et al., 2015)
pretesticular pathway can increase serum FSH, LH,
and testosterone
Vitamin C Vitamin C can improve the motility and morphology (Cyrus et al., 2015)
of spermatozoa
Vitamin E Vitamin E is able to repair oxidizing radicals directly (Yan et al., 2014)
and prevent the process of lipid peroxidation
Beta-Carotene There is a relationship between beta-carotene intake (Talebi et al., 2021)
and sperm motility
Lutein There is a relationship between lutein intake with (Zareba et al., 2013)
sperm motility and normal sperm morphology
Flavonoids Flavonoids can promote hydrogen ions, so they (Jamalan et al., 2016)
can neutralize the toxic effects of these free radicals
and increase motility and morphology of normal
spermatozoa.

Source : Primary Data. 2022


Antioxidants that play a role in deter- parsley. Sources of protein in question include
mining a person’s fertility can be found in legumes, bay shellfish, meat and eel. In addition,
foodstuffs in the form of fruits, vegetables, antioxidants that play a role in determining a
and protein sources. The fruits in question person’s fertility are also found in male date
include watermelon, tomatoes, mango, and flowers, mulberry leaves, sour soup leaves, and
kiwi. The vegetables in question include banana green algae.
blossoms, bamboo shoots, purple carrots, and

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KEMAS 18 (4) (2023) 473-482

TABLE 2. Source of Antioxidants


Source of Antioxidants Types of Antioxidants Reference
Banana Blooms Phenolic (Panyayong and Srikaeo, 2022)
Bamboo Shoots Fenol, Flavonoids, Vitamin C (Singhal et al., 2021)
Spinach Peptide (Fillería et al., 2021)
Pod Polyphenol, Flavonoids, Saponins, (Asati et al., 2022)
isoflavonoid
Purple Carrots Flavonoids (Perez et al., 2022)
Soya bean Isoflavonoiddan peptide (Tkaczewska et al., 2022)
Male Date Flower Polyphenol, flavonoids .(Karra et al., 2020
Parsley Phenolic acid, Flavones, Flavonoid, dan (Ferreira et al., 2022)
Carotenoids
Sorghum seeds Phenolic (Miafo et al., 2022)
Mulberry leaf Phenolic acid, flavonoids, dan alkaloids (Polumackanycz et al., 2021)
Soursop leaf Flavonoids, chlorogenic acid (Leal et al., 2022)
Green algae Phenolic, flavonoids, Vitamin C, Vitamin (S et al., 2022)
D, dan Ferron
Tamarind Papain Hydrolyzate (Bagul et al., 2018)
Purple Head Broccoli Isothiocyanates (Chaudhary et al., 2018)
Watermelon Lycopene (Mahamat et al., 2021)
Tomatoes carotenoids, lycopene, β-carotene, (de Souza et al., 2021)
flavonoids, and anthocyanins
Mango phenolic, glutathione, thiobarbituric (Zapata-Londoño et al., 2020)
acid reactive substances (TBARS), and
8-hydroxydeoxyguanosine
Gulf shell Selenium (Zhang and Yang, 2014)
Se-methyl-seleno-cysteine
(MeSeCys
Kiwi Polyphenol, flavonoids, flavanol, tannins, (Leontowicz et al., 2016)
vitamin C, lutein, zeaxanthin and fiber
Meat Meat contains protein, ferron, vitamin (Pereira and Vicente, 2013)
B12 and other B-complex vitamins, zinc,
selenium and phosphorus.
Eel The moisture, protein, carbohydrate, fat, (Wijayanti and Setiyorini,
ash, vitamin A and vitamin E 2018)
Mushroom Vitamin B3, nicotinic acid, nicotinamide (Çat and Yaman, 2019)

Source : Primary Data. 2022


Glutathione is a natural antioxidant of a cell, protection against oxidative damage,
consisting of three amino acids. Namely endogenous and exogenous detoxification of
cycteine, glutamine, and glycine ( Adeoye et reactive metals and electrophiles, storage and
al., 2018). Glutathione prevented the formation transport of cysteine, as well as for protein
of free oxygen due to the reconstruction of the and DNA synthesis, cell cycle regulation, and
thiol group (-SH)(Palani, 2018). Glutamine is cell differentiation. A reduced glutathione
an amino acid that forms glutathione, prevent system causes cytotoxic and destructive
a decrease in sperm quality, and reduce lesions (Fafula et al., 2017). Consumption of
oxidative stress, inflammation, and apoptosis glutathione food sources is considered capable
(Afolabi et al., 2022). Glutamine prevents NF- of maintaining sperm quality. Mango fruit
kB activation, thereby decreasing transcription contains glutathione, phenolic, TBARS, and
of downstream pro-inflammatory genes, 8-hydroxydeoxyguanosine. Daily consumption
preventing cytokine storms, and DNA damage of mango juice (cv. Azúcar) increases the
(Hamed et al., 2022). Glutathione plays a role antioxidant capacity of plasma (Zapata-
in the maintenance of the thiol redox status Londoño et al., 2020).

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Selenium is vital in growth, immunity, intake (Zareba et al., 2013). Lutein reversed
reproductive system, and endogenous vascular endothelial dysfunction, significantly
antioxidant system support (McLaughlin and upregulated the mRNA and protein expression
Gunderson, 2022). Selenium can increase of SOD2 and GPx1, and down regulated the
semen volume and total sperm motility (Talebi expression of NF-κB p65 and ICAM-1 (Wang
et al., 2021). Selenium modulates DNA repair et al., 2014).
and suppresses testicular toxicity through free Consumed carotenoid sources are
radical targeting. Selenium supplementation recommended to increase the antioxidant
has been shown to reduce the toxicity of non- capacity in the body, so that it can increase
steroidal anti-inflammatory drugs in rat testes the percentage of sperm motility and normal
(Sharma et al., 2020). A higher level of seminal sperm morphology. Tomato is a fruit rich in
selenium is associated with live births and a antioxidants. Tomatoes contain carotenoids,
higher chance of pregnancy (Wu et al., 2020). lycopene, β-carotene, flavonoids, and antho-
Consumption of selenium food sources, such cyanins (de Souza et al., 2021). Parsley also
as meat and bay shellfish, is recommended to contains carotenoids (Ferreira et al., 2022).
improve the quality of spermatozoa, especially Lycopene can be found in watermelon, which
for infertile couples. Meat and shellfish are is 10.46 to 42.83 mg.kg-1 watermelon extract
proven to contain selenium (Pereira and (Mahamat et al., 2021). Kiwi fruit contains
Vicente, 2013; Zhang and Yang, 2014). Lutein (Leontowicz et al., 2016).
Carotenoids are bioactive compounds Zinc is a mineral needed by every
found in many fruits and vegetables. Caro- cell in the body, including the reproductive
tenoids had many types of pigments. Beta- organs. Zinc deficiency causes spermatozoa
cryptoxanthin is a yellow pigment in the abnormalities, such as fibrous sheath hyper-
carotenoid pro-vitamin A. Beta-cryptoxanthin trophy and hyperplasia, axonema disorders,
has antioxidant properties proven to fight free and an abnormal midpiece(Majzoub and
radicals (Brahma and Dutta, 2022). The ability to Agarwal, 2017). Zinc increases total antioxidant
fight free radicals can reduce ROS, so it positively activity (serum SOD/Superoxide Dismutase
affects the percentage of sperm motility (Haeri and -tocopherol)(Omu et al., 2015). The results
et al., 2022). Lycopene is a red pigment in of another study, zinc supplementation for
carotenoids. Lycopene intake is associated 12 weeks showed an increase in the average
with normal spermatozoa morphology. The number of spermatozoa: 14.83 million/mL
percentage of morphologically normal sperm (p-value < 0.01), spermatozoa motility 16.30%
among men in the highest quartile of lycopene (p-value < 0.01), motility fast spermatozoa
intake was 1.7 percent higher than among men 11.96% (p-value < 0.01), and spermatozoa
in the lowest quartile (Zareba et al., 2013). morphology: 4.26% (p-value < 0.001) (Fatima
Lycopene can protect sperm from oxidative et al., 2015). In the pretesticular pathway, zinc
stress and damage to sperm DNA (Babaei can increase serum FSH, LH, and testosterone
et al., 2021). Beta-Carotene is a red-orange (Shahraki et al., 2015). Zinc played a role
pigment in carotenoids. Beta-carotene acts in the amelioration of gonadal dysfunction
as a potent oxidative stress mitigation agent and decreased oxidative stress in the testes
and can modulate oxidative stress through (Mohamad and Hassan, 2014). Zinc modulates
the regulation of ROS turnover (Nishino et the activity of Ca2+, ATPase enzymes and
al., 2017). Beta-carotene intake is positively reduces anti-sperm antibodies, specifically
related to sperm motility (Zareba et al., 2013). Immunoglobulin G (IgG) (Zhao et al., 2016).
Lutein is a natural carotenoid containing many In the testicular pathway, zinc maintains
unsaturated double bonds, which can prevent chromatin stabilization, repairs DNA damage,
free radicals and can produce an antioxidant and plays a role in DNA transcription and
effect (Zhao et al., 2022). Lutein intake is translation (Zhao et al., 2016). In the post-
related to sperm motility. Men with high testicular pathway, zinc regulate the growth
lutein intake had a 4.4 higher percentage of and apoptosis of prostate epithelial cells so
progressive motility than men with low lutein that the prostate can function optimally in

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increasing semen volume (Zhao et al., 2016). antioxidant test results and have a negative
The consumption of foods containing zinc can relationship with the concentration of ROS
be an alternative to taking zinc supplements to (Šola et al., 2018). Flavonoids-contain food is
improve sperm quality. Meat is one of the zinc considered positive on human health (Asati
sources (Pereira and Vicente, 2013). Besides et al., 2022). Parsley consumption can reduce
that, meat is also rich in protein, iron, vitamin oxidized compounds that come from oxidative
B12, other B-complex vitamins, selenium, and processes (Ferreira et al., 2022). Beside parsley,
phosphor (Pereira and Vicente, 2013). other food that contain flavonoid compounds,
Vitamin C, or ascorbic acid, is an anti- such as bamboo shoots (Singhal et al., 2021),
oxidant with the fewest side effects (da Cruz et pods (Asati et al., 2022), purple carrots (Perez
al., 2018). Vitamin C can improve the motility et al., 2022), mulberry leaves (Polumackanycz
and morphology of spermatozoa (Cyrus et et al., 2021), tomatoes (de Souza et al., 2021),
al., 2015). Vitamin C neutralizes free radicals, and kiwi (Leontowicz et al., 2016).
so it can prevent and/or reduce the presence NAM or niacin or vitamin B3 is a type of B
of ROS (Agarwal et al., 2014). Vitamin C is vitamin that plays a role in enzymatic reactions
able to captured hydroxyl free radicals by in carbohydrate, fat, and protein metabolism
donating a single electron (Zhao et al., 2013). formed from nicotinic acid and nicotinamide
Vegetables and fruits serve as natural sources of (Çat and Yaman, 2019). Niacin can capture free
vitamin C intake. Vitamin C is found in kiwi radicals and reduce ROS (El Sheikh et al., 2020).
fruit (Leontowicz et al., 2016), bamboo shoots The level of NAM in follicular fluid is associated
(Singhal et al., 2021), and green algae (S et al., with the development of larger follicles, and
2022). the level of niacin is also associated with the
Vitamin E is a fat-soluble antioxidant. oocyte maturation and fertilization rate (Guo
Vitamin E can repair oxidizing radicals directly et al., 2022). Consumption of mushrooms can
and prevent the process of lipid peroxidation contribute to the need for vitamin B3 as much
(Yan et al., 2014). Spermatozoa DNA fragmen- as 5.384 mg/100g, consisting of 66% nicotinic
tation can be reduced by taking vitamin E, acid and 34% nicotinamide (Çat and Yaman,
thus increases the morphology of normal 2019).
spermatozoa(Egwurugwu et al., 2013). Vitamin Phenol is one type of phenolic compound
E can increase semen volume and sperm motility with a simple group, which is beneficial for the
(Muhammad, 2017). Malondialdehyde (MDA) body because of its antioxidant properties that
levels decreased significantly in the vitamin C can protect tissues from oxidative damage.
and E. supplementation groups. MDA levels are Carvacrol or also known as monoterpenoid
markers of oxidative stress. Decreased MDA phenol, is a part of phenol that has high activity
levels is along with decreased oxidative stress as an antioxidant, increased antioxidant
(Rusiani et al., 2019). Consumption of sources defenses lead to increased immune system
of vitamin E is recommended, especially for response (Hashemipour et al., 2014). Carvacrol
individuals who had oxidative stress. One has a positive impact on infertility treatment
source of vitamin E is eel. Vitamin E content of because carvacrol plays a role in the treatment
the wild eel was 0.21%, and 0.224% of cultural of ischemia-reperfusion ovarian injury and
eel (Wijayanti and Setiyorini, 2018). infertility (Sahin et al., 2022). Some plants
Flavonoids are one of a compounds group. that contain carvacrol include banana blossom
It can be used as anticancer, antidepressant, and (Panyayong and Srikaeo, 2022), bamboo shoots
antioxidant. Flavonoids can be found in plant (Singhal et al., 2021), pod(Asati et al., 2022),
extracts (Mouradov and Spangenberg, 2014). male date flower(Karra et al., 2020), parsley
Flavonoids can neutralize the toxic effects of free (Ferreira et al., 2022), sorghum seeds(Miafo
radicals because they can encourage hydrogen et al., 2022), mulberry leaf(Polumackanycz
ions to increase the motility and morphology et al., 2021), green algae(S et al., 2022),
of normal spermatozoa (Jamalan et al., 2016). mango(Zapata-Londoño et al., 2020) and kiwi
Flavonoids have a strong relationship with the (Leontowicz et al., 2016).

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Conclusion A., & Kazemi-Darabadi, S., 2021. Lycopene


Antioxidants can increase fertility in Protects Sperm from Oxidative Stress in the
both men and women. Most antioxidants play Experimental Varicocele Model. Food Sci.
Nutr., 9, pp.6806–6817.
a role in improving sperm quality through the
Bagul, M.B., Sonawane, S.K., & Arya, S.S., 2018.
ROS suppression. Antioxidants for increasing
Bioactive Characteristics and Optimization
male fertility include glutathione, selenium, of Tamarind Seed Protein Hydrolysate
carotenoids (beta-cryptoxanthin, lycopene, for Antioxidant-Rich Food Formulations.
beta-carotene, and lutein), zinc, vitamin C, Biotech, 8, pp.1–8.
vitamin E, and flavonoids. Only 2 antioxidants Bai, K., Xu, W., Zhang, J., Kou, T., Niu, Y., Wan,
play a role in determining female fertility in X., Zhang, L., Wang, C., & Wang, T., 2016.
this review, namely NAM and carvacrol. These Assessment of Free Radical Scavenging
antioxidants can be found in several sources Activity of Dimethylglycine Sodium Salt
antioxidants. Sources of antioxidants in the form and Its Role in Providing Protection Against
Lipopolysaccharide- Induced Oxidative
of fruit, namely watermelon, tomatoes, mango,
Stress in Mice. PLoS One, 11, pp.1–17.
and kiwi. Sources of antioxidants in vegetables,
Bakhtiyar, K., Beiranvand, R., Ardalan, A.,
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Content of Wild and Cultured Eel (Anguilla

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